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Background: Once aprotinin was no longer available for clinical use, ε-aminocaproic acid (EACA) and tranexamic acid became the only two options for antifibrinolytic therapy. We compared aprotinin and EACA with respect to their blood-sparing efficacy and other major clinical outcome criteria in infants undergoing cardiac surgery., Methods: We retrospectively analysed data from a large consecutive cohort of infants (n=227) aged 31-365 days undergoing primary cardiac surgery requiring cardiopulmonary bypass encompassing the transition from aprotinin to EACA (aprotinin n=88, EACA n=139); all other aspects including the medical team and departmental protocols remained unchanged. The primary outcome was postoperative blood loss measured as chest tube output (CTO). Secondary outcome parameters were transfusion requirements, reoperation due to bleeding, renal, vascular, and neurological complications, and in-hospital mortality., Results: CTO was significantly higher in the EACA patients {aprotinin 18 (13-27) ml kg(-1) 24 h(-1), EACA 23 (15-37) ml kg(-1) 24 h(-1) [mean (inter-quartile range)], P=0.001}, but transfusion requirements and donor exposures were not significantly different. A sensitivity analysis strengthened our finding that the increased blood loss in the EACA group was attributable to lower efficacy of EACA. There were no significant differences in the other clinical outcome measures., Conclusions: CTO was lower in aprotinin-treated patients. Nonetheless, EACA remains a suitable substitute without measurable differences in other clinical outcome criteria.

Background: With the withdrawal of aprotinin from worldwide marketing in November 2007, many institutions treating patients at high risk for hyperfibrinolysis had to update their therapeutic protocols. At our institution, the standard was switched from aprotinin to ε-aminocaproic acid (EACA) in all patients undergoing cardiac surgery with extracorporeal circulation including neonates. Although both antifibrinolytic medications have been used widely for many years, there are few data directly comparing their blood-sparing effect and their side-effects especially in neonates., Methods: Perioperative data from 235 neonates aged up to 30 days undergoing primary cardiac surgery were analysed. Between July 1, 2006 and November 5, 2007, all patients (n=95) received aprotinin. Starting November 6, 2007 until December 31, 2009, all patients (n=140) were treated with EACA. The primary outcome criterion was blood loss; secondary outcome criteria were transfusion requirements, renal, vascular, and neurological complications and also in-hospital mortality., Results: All descriptive and intraoperative data variable were similar. Blood loss was significantly higher in the EACA group (P=0.001), but there was no difference in the rate of re-operation for bleeding (P=0.218) nor the number of transfusions. There were no differences in the incidences of postoperative renal, neurological, and vascular events or in-hospital mortality., Conclusions: In neonatal patients undergoing cardiac surgery, the switch to EACA treatment led to a higher postoperative blood loss. However, there were no differences in transfusion requirements or major clinical outcomes.

Objective: Recently, the safety of aprotinin administration during open-heart surgery has been debated. The aim of the study was to compare the blood sparing effect and the side effects of aprotinin and tranexamic acid in paediatric cardiac surgery patients., Methods: Perioperative data of 199 consecutive patients weighing less than 20kg undergoing open-heart cardiac surgery were prospectively collected between September 2005 and June 2006. During the first 5 months, 85 patients received aprotinin (group A); in the next 5 months, 114 patients were treated with tranexamic acid (group T). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained unchanged. Postoperative complications and in-hospital and 1-year mortality were considered as outcome parameters., Results: The descriptive parameters and the intraoperative parameters were well comparable in the two groups. The blood loss was significantly lower in group A compared to group T at 6h [55 (35-82.5) vs 70 (45-100)ml, p=0.031], but not at 12 and 24h after operation. The incidence [9 (11%) vs 25 (22%), p=0.035] and the amount of red blood cell transfusion during the first 24h after surgery were also significantly lower in group A (0.1+/-0.4 vs 0.3+/-0.6 unit, p=0.036). There were significantly less rethoracotomies in group A [2 (2.4%) vs 11 (9.6%), p=0.039]. We found no difference in the incidence of the postoperative complications and in-hospital and 1-year mortality. There was a tendency for a higher incidence of seizures in group T [4 (3.5%) vs 0 (0%), p=0.14]., Conclusions: Aprotinin administration bears no additional risks compared to tranexamic acid and it has a stronger blood sparing effect in paediatric cardiac surgery. There were fewer rethoracotomies and less postoperative red blood cell transfusion in patients who received aprotinin.

Background: Our aim was to investigate postoperative complications and mortality after administration of aprotinin compared to tranexamic acid in an unselected, consecutive cohort., Methods: Perioperative data from consecutive cardiac surgery patients were prospectively collected between September 2005 and June 2006 in a university-affiliated clinic (n = 1188). During the first 5 mo, 596 patients received aprotinin (Group A); in the next 5 mo, 592 patients were treated with tranexamic acid (Group T). Except for antifibrinolytic therapy, the anesthetic and surgical protocols remained unchanged., Results: The pre- and intraoperative variables were comparable between the treatment groups. Postoperatively, a significantly higher incidence of seizures was found in Group T (4.6% vs 1.2%, P < 0.001). This difference was also significant in the primary valve surgery and the high risk surgery subgroups (7.9% vs 1.2%, P = 0.003; 7.3% vs 2.4%, P = 0.035, respectively). Persistent atrial fibrillation (7.9% vs 2.3%, P = 0.020) and renal failure (9.7% vs 1.7%, P = 0.002) were also more common in Group T, in the primary valve surgery subgroup. On the contrary, among primary coronary artery bypass surgery patients, there were more acute myocardial infarctions and renal dysfunction in Group A (5.8% vs 2.0%, P = 0.027; 22.5% vs 15.2%, P = 0.036, respectively). The 1-yr mortality was significantly higher after aprotinin treatment in the high risk surgery group (17.7% vs 9.8%, P = 0.034)., Conclusion: Both antifibrinolytic drugs bear the risk of adverse outcome depending on the type of cardiac surgery. Administration of aprotinin should be avoided in coronary artery bypass graft and high risk patients, whereas administration of tranexamic acid is not recommended in valve surgery.

Objective: To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass (CPB)., Design: Randomized, double-blind, placebo-controlled study., Setting: University-affiliated cardiac center., Participants: Twenty patients scheduled for coronary artery bypass graft surgery., Interventions: In group A patients (n = 10), high-dose aprotinin was administered (2 x 106 KIU pre-CPB, 2 x 10(6) KIU in prime, 500,000 KIU/hr during CPB). In group C patients (n = 10), placebo was used instead. Proinflammatory interleukin (IL)-6, anti-inflammatory IL-1-receptor antagonist, and clinical parameters were measured 8 times perioperatively. The values are presented as mean +/- SEM., Measurements and Main Results: Four hours after CPB, IL-6 concentration reached the maximum value, being significantly lower in group A patients as compared with group C patients (615 +/- 62 pg/mL v 1,409 +/- 253 pg/mL; p = 0.019). On the first postoperative day, the concentration of IL-6 in group A patients remained lower (219 +/- 24 pg/mL v 526 +/- 123 pg/mL; p = 0.015). In contrast, IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB (13,857 +/- 4,264 pg/mL v 5,675 +/- 1,832 pg/mL; p = 0.03). Total postoperative blood loss was lower in group A patients as compared with group C patients (648 +/- 64 mL v 1,284 +/- 183 mL; p = 0.002)., Conclusions: High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss. The anti-inflammatory reaction was significantly enhanced in these patients, which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin.

Objective: To discover the possible effects of methylprednisolone on the systemic inflammatory response during aprotinin treatment., Design: Randomized, double-blinded study., Setting: University-affiliated heart center., Participants: Fifty-two patients scheduled for elective coronary artery bypass grafting., Interventions: In the methylprednisolone group (n = 26), 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass (CPB). The 26 control patients received a placebo instead. High-dose aprotinin was administered to all participants., Measurements and Main Results: After CPB, the concentration of the proinflammatory cytokines, interleukin-6 and interleukin-8, was significantly less in the methylprednisolone group. The anti-inflammatory interleukin-10 concentration was, in contrast, greater. After CPB, PaO2 was greater in the methylprednisolone group (245+/-17 v 195+/-16 mmHg). Dynamic pulmonary compliance was also greater, whereas the alveolar-arterial oxygen difference was less (376+/-17 v 428+/-16 mmHg). On arrival in the intensive care unit, the oxygen delivery index was greater in the methylprednisolone group (62+/-2.7 v 54+/-2.3 mL/min/m2) and the oxygen extraction rate was less (25%+/-0.02% v 30%+/-0.02%). After CPB, the cardiac index was significantly greater in the methylprednisolone group (4.1+/-0.2 v 3.6+/-0.2 L/min/m2). These patients had less blood loss postoperatively (616+/-52 v 833+/-71 mL; p = 0.017) and a greater urine output (8,015+/-542 v 6,417+/-423 mL/24 h; p = 0.024)., Conclusion: The use of methylprednisolone attenuates the systemic inflammatory response during aprotinin treatment and improves clinical outcome parameters.